Diisopropylethylamine → HCID 178481750, compound

Participants

Reaction Steps

A flask was charged with 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (250 mg, 0.57 mmol), 3-aminocyclobutanol hydrochloride (98 mg, 0.79 mmol) and DMF (2.8 mL). N,N-diisopropylethylamine (266 mg, 0.36 mL, 2.06 mmol) was added followed by HATU (237 mg, 0.62 mmol). The yellow solution was stirred at room temperature overnight (a precipitate was formed). The reaction mixture was diluted with water and petroleum ether. The suspension was filtered. The solid was washed with water and a little petroleum ether. The resulting off-white powder was dried under high vacuum. The mixture of cis- and trans-product (265 mg off-white powder) was submitted for further separation by SFC chromatography (KROMASIL OD 3×25 cm, 25% MeOH/CO2+0.1% Triethylamine) to afford 139 mg (48%) 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (cis-3-hydroxy-cyclobutyl)-amide as an off-white solid and 102 mg (35%) 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (trans-3-hydroxy-cyclobutyl)-amide as an off-white solid.

Provenance & Evidence